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. 1998 Dec;43(6):783–790. doi: 10.1136/gut.43.6.783

Elevated plasma leptin concentrations in early stages of experimental intestinal inflammation in rats

M Barbier 1, C Cherbut 1, A Aube 1, H Blottiere 1, J Galmiche 1
PMCID: PMC1727345  PMID: 9824605

Abstract

Background—Although leptin, an adipocyte derived hormone which regulates food intake and energy balance, is released after injections of tumour necrosis factor (TNF) and interleukin 1,plasma concentrations have not been characterised in chronic inflammation. Leptin may contribute to the anorexia and body weight loss associated particularly with the acute stages of inflammatory bowel disease. 
Aims—To investigate plasma leptin concentrations during the time course of intestinal inflammation in different animal models. 
Methods—Plasma leptin was measured at different time points in rats with trinitrobenzene sulphonic acid (TNBS) induced colitis, indomethacin induced ileitis, or endotoxic shock caused by lipopolysaccharide (LPS). Systemic TNF-α was also measured during acute inflammation. 
Results—Plasma leptin concentrations increased fourfold eight hours after induction of TNBS colitis (p<0.0001) and twofold after administration of ethanol alone (p<0.02). Plasma leptin responses throughout the first post-treatment day were correlated with myeloperoxidase activity and gross damage scores. Similar leptin overexpression was observed in indomethacin induced ileitis and in rats with endotoxic shock. Plasma concentrations were lower in TNBS treated rats than in controls on day 5 before reaching a similar concentration on day 14. Anorexia and body weight loss were observed during the first four days post-TNBS. A significant increase in systemic TNF-α was only detected in LPS treated rats. 
Conclusion—Elevated plasma leptin concentrations, correlated with the degree of inflammation and associated with anorexia, were induced in rats during the early stages of experimental intestinal inflammation but proved transient; this might account for discrepancies in recent results concerning concentrations in patients with inflammatory bowel diseases. 



Keywords: leptin; inflammatory bowel disease; experimental rat intestinal inflammation; tumour necrosis factor; endotoxic shock; anorexia

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Figure 1 .

Figure 1

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Daily (24 h) food intake (A) and body weight (B) for 13 days after intracolonic administration (arrow) of TNBS or saline in rats. Day 0 represents pretreatment baseline. Values are means (SEM). Significantly different between saline and TNBS, *p<0.05, ***p<0.001, †p<0.0001. 


Figure 2 .

Figure 2

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Changes in plasma leptin concentrations after intracolonic administration (arrow) of TNBS, ethanol, or saline in rats on days 1 and 2 (A), days 5 and 6 (B), and days 14 and 15 (C). Values are means (SEM). Significantly different from saline: *p<0.05, **p<0.01, ***p<0.001, †p<0.0001. Significantly different from TNBS, ‡p<0.05, §p<0.001. 


Figure 3 .

Figure 3

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Correlation of areas under the curve (AUC) of changes in plasma leptin concentrations throughout the first day post-TNBS, post-ethanol, and post-saline with MPO activity measured at 24 hours post-treatment. Each point represents the value of one rat (n=17), p<0.0001. 


Figure 4 .

Figure 4

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Changes in plasma leptin concentrations on days 2 and 3 in the indomethacin induced ileitis model. All rats were subcutaneously injected with indomethacin (n=7) or saline (n=6) daily at 24 hour intervals, the second injection representing day 1. Values are means (SEM). *Significantly different from saline, p<0.05. 


Figure 5 .

Figure 5

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Changes in plasma leptin concentrations on the first day after intraperitoneal administration of lipopolysaccharide (n=6) or saline (n=6) in rats. Values are means (SEM). Significantly different from saline, *p<0.05, **p<0.01, †p<0.001. 


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